Pharmacokinetic and Pharmacodynamic Study of Bococizumab Alone and When Combined With Recombinant Human Hyaluronidase

NCT02667223 | Terminated Phase 1

• 2 other identifiers: B14810512015-003568-36
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, single-dose, randomized, dose escalation study in healthy and hypercholesterolemic subjects. Each subject will receive 1 of 5 treatments as a single subcutaneous injection. Subjects will remain confined at the research clinic for approximately 2 days. After discharge, subjects will return to the research clinic 15 times during 12 weeks.

Conditions

Healthy; Hypercholesterolemia

Keywords

pharmacokinetics; pharmacodynamics; RN316; recombinant human hyaluronidase

Outcome Measures

Primary Outcomes (2)

• AUCinf of bococizumab

  Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞), if data permits (otherwise AUClast will be used).

  Day 1 - Day 85

• Cmax of bococizumab

  Maximum Observed Plasma Concentration (Cmax)

  Day 1 - Day 85

Secondary Outcomes (14)

• Tmax

  Day 1 - Day 85

• CL/F

  Day 1 - Day 85

• Vz/F

  Day 1 - Day 85

• t1/2

  Day 1 - Day 85

• LDL-C at Week 4

  Baseline to Week 4

Study Arms (5)

Cohort 1: bococizumab 150 mg + rHuPH20

EXPERIMENTAL

bococizumab 150 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

Biological: Cohort 1: bococizumab 150 mg + rHuPH20

Cohort 2: bococizumab 300 mg

ACTIVE COMPARATOR

bococizumab 300 mg administered subcutaneously to healthy volunteers

Biological: Cohort 2: bococizumab 300 mg

Cohort 3: bococizumab 300 mg + rHuPH20

EXPERIMENTAL

bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

Biological: Cohort 3: bococizumab 300 mg + rHuPH20

Cohort 5: bococizumab 450 mg + rHUPH20

EXPERIMENTAL

bococizumab 450 mg co-mixed with rHuPH20 and administered subcutaneously to healthy volunteers

Biological: Cohort 5: bococizumab 450 mg + rHuPH20

Cohort 4: bococizumab 300 mg + rHuPH20

EXPERIMENTAL

bococizumab 300 mg co-mixed with rHuPH20 and administered subcutaneously to subjects with hypercholesterolemia receiving a statin

Biological: Cohort 4: bococizumab 300 mg + rHuPH20

Interventions

Cohort 1: bococizumab 150 mg + rHuPH20 BIOLOGICAL

bococizumab 150 mg + rHuPH20 administered SC to healthy volunteers

Cohort 1: bococizumab 150 mg + rHuPH20

Cohort 2: bococizumab 300 mg BIOLOGICAL

bococizumab 300 mg administered SC to healthy volunteers

Cohort 2: bococizumab 300 mg

Cohort 3: bococizumab 300 mg + rHuPH20 BIOLOGICAL

bococizumab 300 mg + rHuPH20 administered SC to healthy volunteers

Cohort 3: bococizumab 300 mg + rHuPH20

Cohort 5: bococizumab 450 mg + rHuPH20 BIOLOGICAL

bococizumab 450 mg + rHuPH20 administered SC to healthy volunteers

Cohort 5: bococizumab 450 mg + rHUPH20

Cohort 4: bococizumab 300 mg + rHuPH20 BIOLOGICAL

bococizumab 300 mg + rHuPH20 administered SC to subjects with hypercholesterolemia receiving a statin

Cohort 4: bococizumab 300 mg + rHuPH20

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy and hypercholesterolemic subjects between the ages of 18 and 65 years.
• Healthy subjects must have fasting LDL-C \>/= 70 to \</= 190 mg/dL at two qualifying visits.
• Hypercholesterolemic subjects must be on a stable daily dose of statin for at least 45 days before dosing and fasting LDL-C must be \>/= 70 mg/dL.

You may not qualify if:

• Use of prescription or non-prescription drugs within 7 days or 5 half-lives (whichever) is longer prior to the first dose of study medication. For hypercholesterolemic subjects the use of statin class medication is allowed.
• Prior exposure to bococizumab (also known as PF-04950615 or RN316) or other investigational PCSK9 inhibitors.
• Treatment with monoclonal antibodies within 6 months or 5 half-lives (whichever is longer) before dosing.

Sponsors & Collaborators

• Pfizer: lead
• Halozyme Therapeutics: collaborator

Study Sites (1)

Pfizer Clinical Research Unit

Brussels, B-1070, Belgium

Location

Related Publications (1)

• Bass A, Plotka A, Mridha K, Sattler C, Kim AM, Plowchalk DR. Pharmacokinetics, pharmacodynamics, and safety of bococizumab, a monoclonal antibody against proprotein convertase subtilisin/kexin type 9, in healthy subjects when administered in co-mixture with recombinant human hyaluronidase: A phase 1 randomized trial. Health Sci Rep. 2018 Jul 18;1(9):e61. doi: 10.1002/hsr2.61. eCollection 2018 Sep.

  PMID: 30623096 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 28, 2016
• Study Start: February 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: October 21, 2016

Record last verified: 2016-10

Locations

BE (1)